RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Zoledronate may prevent bone loss in patients who are receiving letrozole. It is not yet known which schedule of zoledronate is more effective in preventing bone loss in patients with breast cancer.

PURPOSE: This randomized phase III trial is studying two different schedules of zoledronate to compare how well they work in preventing bone loss in postmenopausal women who are receiving letrozole for stage I, stage II, or stage IIIA breast cancer.

A Randomized, Controlled, Open-Label Trial of Empiric Prophylactic vs. Delayed Use of Zoledronic Acid for Prevention of Bone Loss in Postmenopausal Women With Breast Cancer Initiating Therapy With Letrozole After Tamoxifen

In both arms, treatment continues for up to 5 years in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 550 patients (275 per treatment arm) will be accrued for this study within 28 months.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Female

Accepts Healthy Volunteers:

No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of breast cancer

Stage I, II, or IIIA disease

Completed ≤ 6 years of adjuvant tamoxifen therapy

Total baseline lumbar spine or femoral neck bone mineral density T-score below -2.0 standard deviation (e.g., a patient with a T-score of -2.1 in ineligible; a patient with a T-score of -1.9 is eligible)

No clinical or radiological evidence of recurrent or metastatic disease

Hormone receptor status:

Estrogen receptor- and/or progesterone receptor-positive

PATIENT CHARACTERISTICS:

Age

Postmenopausal

Sex

Female

Menopausal status

Postmenopausal, defined by 1 of the following:

Over 55 years of age with cessation of menses

55 years of age and under with spontaneous cessation of menses for > 1 year

55 years of age and under with spontaneous cessation of menses for ≤ 1 year, but amenorrheic (e.g., spontaneous or secondary to hysterectomy) with postmenopausal estradiol levels (< 5 ng/dL)

No known hypersensitivity to zoledronate or other bisphosphonates, letrozole, calcium, or cholecalciferol (vitamin D)

No mental illness that would preclude giving informed consent

No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

No other non-malignant systemic disease

No clinical or radiologic evidence of existing fracture in the lumbar spine and/or total hip

No history of fracture with low intensity or not associated with trauma

No contraindication to spinal dual energy x-ray absorptiometry (DEXA) due to any of the following:

History of surgery at the lumbosacral spine, with or without implantable devices

Scoliosis with a Cobb angle > 15° at the lumbar spine

Immobility, hyperostosis, or sclerotic changes at the lumbar spine

Evidence of sufficient sclerotic abdominal aorta that would interfere with DEXA scan

Any disease of the spine that would preclude proper acquisition of a lumbar spine DEXA

Considered reliable

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

No concurrent chemotherapy

Endocrine therapy

See Disease Characteristics

Prior parathyroid hormone allowed provided it was not administered for > 1 week

More than 6 months since prior anabolic steroids or growth hormone

More than 12 months since prior endocrine therapy (including estrogen) except for the following:

Tamoxifen

Insulin

Oral hypoglycemics

Thyroid hormone

Steroid inhalers

More than 12 months since prior systemic corticosteroids except short-term corticosteroids to prevent or treat chemotherapy-induced nausea and vomiting or acute respiratory illness

Concurrent short-term corticosteroids allowed

No other concurrent hormonal therapy

No concurrent parathyroid hormone

Radiotherapy

Not specified

Surgery

Not specified

Other

Prior systemic sodium fluoride allowed provided it was not administered for > 3 months within the past 2 years

More than 3 weeks since prior oral bisphosphonates

More than 2 weeks since prior and no concurrent drugs known to affect the skeleton (e.g., calcitonin, mithramycin, or gallium nitrate)

More than 30 days since prior systemic investigational drugs and/or devices

More than 7 days since prior topical investigational drugs

No prior IV bisphosphonates

No prior aromatase inhibitor therapy

No concurrent calcitonin, sodium fluoride, or Tibolone

No other concurrent anticancer therapy

No other concurrent bisphosphonates

No other concurrent investigational drugs or devices

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00107263